7-METHOXY-2-NITRONAPHTHO[2,1-B]FURAN (R7000)-INDUCED MUTATION SPECTRUM IN THE LACI GENE OF ESCHERICHIA-COLI - INFLUENCE OF SOS MUTAGENESIS

The mutagenic specificity of 7-methoxy-2-nitronaphtho[2,1-b]furan (R70 00), a very potent genotoxic 2-nitrofuran, was investigated in the lad gene of E. coli. To analyze the influence of SOS-mutagenesis on R7000 -induced mutations, 86 and 84 LacI(-) mutants were respectively isolat ed from umuC(+) and umuC strains, Treatment of bacteria with increasin g concentrations of R7000, affected 2-4 times more the survival rate i n the umuC context, as compared to umuC(+). 80% of all mutations occur red primarily at G:C base pairs and were substitution events and singl e-base frameshifts (-1) in the same proportions, The six possible subs titution events were observed in both strains, In the umuC(+) context, they were dominated by G:C-->T:A transversions, 38% of substitutions at G:C base pairs occurred in the consensus sequence 5'TGGCG3' or 5'TG GC3' where the G was mutated, When umuC was deficient C:C-->C:G transv ersions were mainly observed, The proportions of substitution mutation s were very similar to those that have been reported for apurinic (AP) sites, suggesting strongly that one mechanism for R7000-induced mutat ions is the formation of intermediate abasic sites that serve as a sub strate for error-prone repair, Single frameshift events consisted esse ntially of deletions of one (G:C) base pair in runs of contiguous G or C residues, Frameshift frequency increased with the length of the rei terated sequence, suggesting a strand-slippage process, Other mutation al classes were recovered to a lower extent, including double-base fra meshifts and large deletions, In addition, 10% of the mutants presente d two proximate mutations, Comparison of the mutations induced by R700 0 in the umuC(+)/umuC backgrounds suggests an influence of the umuC pr oduct on strand specificity of R7000-induced mutations, particularly i n the case of frameshift events.